A relevant panel of human uveal melanoma xenografts directly established from primary and/or metastatic patient’s tumor for pharmacological preclinical assays

Purpose Human cancer xenografts transplanted into immunodeficient mice constitute a useful preclinical tool for testing new agents and protocols and for further exploration of the biological basis of drug responses. The aim of this study was then to develop, establish, and characterize an in vivo panel of xenografts directly obtained from uveal melanoma patients. Methods Samples obtained from primary tumors after enucleation or from liver metastases, were subcutaneously xenografted into immunocompromised mice. A characterization of the xenografts growing into mice was then performed and compared to originated tumors, including histopathological, genetic (karyotype or FISH, and CGH-array), and molecular assays. Results Thirty-seven xenografts have been obtained among 95 patient’s tumor sample transplantations in which 10 have still grown after at least three transplantations in mice and have been characterized. Pathological analyses of these ten xenografts confirmed the diagnosis of uveal melanoma and showed, for the five models derived from primary tumors, similar chromosome 3status. Bcl-2 protein was overexpressed in all but 2 xenografts. NA17 and Melan-A antigen expressions were positive in all tested samples, tyrosinase antigen expression was positive in all but 2 xenografts, and MAGE- (1/2/3/4/6/10), LAGE-1, and MAGE-C2 antigens expression were negative in all studied cases. Conclusion Our in vivo human uveal melanoma xenografts present the same histopathological and genomic characteristics of the patient’s originated tumors. This observation supports the use of our panel for pharmacological preclinical evaluations that could serve as a bridge linking pre-clinical and clinical research, and drug development.